Polymeric Nanoparticles with a Glutathione‐Sensitive Heterodimeric Multifunctional Prodrug for In Vivo Drug Monitoring and Synergistic Cancer Therapy

Polymeric micelle‐based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. A polymeric nanomedicine has now been engineered that possesses an ultrahigh loading (59 %) of a glutathione (GSH)‐sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co‐deliver two synergistic drugs to tumors. An HDMP comprising of chemotherapeutic camptothecin (CPT) and photosensitizer 2‐(1‐hexyloxyethyl)‐2‐devinyl pyropheophorbide‐α (HPPH) was conjugated via a GSH‐cleavable linkage. The intrinsic fluorogenicity and label‐free radio‐chelation (⁶⁴Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, HDMP significantly improves drug delivery to tumors. The high synergistic therapeutic efficacy of HDMP‐loaded NPs highlights the rational design of HDMP, and presents exciting opportunities for polymer NP‐based drug delivery.     

DOPC‐Detergent Conjugates: Fusogenic Carriers for Improved In Vitro and In Vivo Gene Delivery

Phospholipid‐detergent conjugates are proposed as fusogenic carriers for gene delivery. Eleven compounds are prepared and their properties are investigated. The ability of the conjugates to promote fusion with a negatively charged model membrane is determined. Their DNA delivery efficiency and cytotoxicity are assessed in vitro. Lipoplexes are administered in the mouse lung, and transgene expression Indeterminate inflammatory activity are measured. The results show that conjugation of 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC) with C₁₂E₄ produces a carrier that can efficiently deliver DNA to cells, with negligible ­associated toxicity. Fusogenicity of the conjugates shows good correlation with in vitro transfection efficiency and crucially depends on the length of the polyether moiety of the detergent. Finally, DOPC‐C₁₂E₄ reveals highly potent for in vivo DNA delivery and favorably compares to GL67A, the current golden standard for gene delivery to the airway, opening the way for further promising developments.

     

In Vivo Effect of Resveratrol-Loaded Solid Lipid Nanoparticles to Relieve Physical Fatigue for Sports Nutrition Supplements

Resveratrol (RSV) is a natural flavonoid polyphenol compound extracted from the plants which shows various biological activities. However, the clinical application of RSV is limited by its poor aqueous solubility, rapid metabolism and poor bioavailability. In this study, resveratrol-loaded solid lipid nanoparticles (RSV- SLNs) was design as a nano-antioxidant against the physical fatigue. The resultant RSV-SLNs were characterized by photon correlation spectroscopy (PCS), transmission electron micrographs (TEM), zeta potential, differential scanning calorimetry (DSC) and Raman spectroscopy pattern. Furthermore, the in vivo anti-fatigue effect assays showed that RSV-SLNs prolonged the mice exhausted time and running distance. The biochemical parameters of blood related to fatigue suggested that RSV-SLNs have potential applications to improve the antioxidant defense of the mice after extensive exercise and confer anti-fatigue capability. Furthermore, the molecular mechanisms of antioxidant by RSV-SLNs supplementation was investigated through the analysis of silent information regulator 2 homolog 1 (SIRT1) protein expression, which demonstrated that it could downregulate the expression of SIRT1 and increase autophagy markers, microtubule-associated protein 1 light chain 3-II (LC3-II) and sequestosome-1 (SQSTM1/p62). These results reveal that the RSV-SLNs may have great potential used as a novel anti-fatigue sports nutritional supplement.     

Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box–Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity.     

Chitosan Nanoparticle-Based System: A New Insight into the Promising Controlled Release System for Lung Cancer Treatment

Lung cancer has been recognized as one of the most often diagnosed and perhaps most lethal cancer diseases worldwide. Conventional chemotherapy for lung cancer-related diseases has bumped into various limitations and challenges, including non-targeted drug delivery, short drug retention period, low therapeutic efficacy, and multidrug resistance (MDR). Chitosan (CS), a natural polymer derived from deacetylation of chitin, and comprised of arbitrarily distributed β-(1-4)-linked d-glucosamine (deacetylated unit) and N-acetyl-d-glucosamine (acetylated unit) that exhibits magnificent characteristics, including being mucoadhesive, biodegradable, and biocompatible, has emerged as an essential element for the development of a nano-particulate delivery vehicle. Additionally, the flexibility of CS structure due to the free protonable amino groups in the CS backbone has made it easy for the modification and functionalization of CS to be developed into a nanoparticle system with high adaptability in lung cancer treatment. In this review, the current state of chitosan nanoparticle (CNP) systems, including the advantages, challenges, and opportunities, will be discussed, followed by drug release mechanisms and mathematical kinetic models. Subsequently, various modification routes of CNP for improved and enhanced therapeutic efficacy, as well as other restrictions of conventional drug administration for lung cancer treatment, are covered.     

Use of Three‐Dimensional Arterial Models To Predict the In Vivo Behavior of Nanoparticles for Drug Delivery

Nanomaterials have been widely used for applications in biomedical fields and could become indispensable in the near future. However, since it is difficult to optimize in vivo biological behavior in a 3D environment by using a single cell in vitro, there have been many failures in animal models. In vitro prediction systems using 3D human‐tissue models reflecting the 3D location of cell types may be useful to better understand the biological characteristics of nanomaterials for optimization of their function. Herein we demonstrate the potential ability of 3D engineered human‐arterial models for in vitro prediction of the in vivo behavior of nanoparticles for drug delivery. These models enabled optimization of the composition and size of the nanoparticles for targeting and treatment efficacy for atherosclerosis. In vivo experiments with atherosclerotic mice suggested excellent biological characteristics and potential treatment effects of the nanoparticles optimized in vitro.     

Insulin-Loaded SLN Prepared with the Emulsion Dilution Technique: In Vivo Tracking of Nanoparticles after Oral Administration to Rats

Insulin-loaded solid lipid nanoparticles (SLN) were prepared according to a solvent dilution method from O/W emulsions using isovaleric acid as organic phase. Insulin was derivatized with fluorescein isothyocianate (FITC) obtaining a fluorescent marker to be used in in vivo experiments. FITC-insulin and native insulin–loaded SLN were quite similar with regard to their mean sizes and encapsulation efficiency. SLN intestinal uptake was then investigated administering FITC-insulin loaded SLN on healthy male Wistar rats. Significant drug accumulation within intestinal lymphatic system was recovered, but the immune system seems to play an important role in SLN degradation: further studies are necessary to improve the results on blood glucose level.